4-pyridin-4-yl-2,3-dihydro-1H-indole | 90679-14-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-pyridin-4-yl-2,3-dihydro-1H-indole
• 英文别名: 4-(Pyridin-4-yl)indoline
• CAS: 90679-14-4
• 化学式: C₁₃H₁₂N₂
• 分子量: 196.252
• InChiKey: ZIXCTOFSLZTNKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate 、 4-pyridin-4-yl-2,3-dihydro-1H-indole 在 sodium hydroxide 、 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 以70%的产率得到6-(morpholin-4-yl)-2-{2-oxo-2-[4-(pyridin-4-yl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-one
  参考文献：
  名称：

  Discovery and Optimization of Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatment of Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers

  摘要：

  Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3K beta in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3K beta-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3K beta inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110 beta with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.

  DOI：

  10.1021/jm401642q
• 作为产物：
  描述：

  4-溴二氢吲哚 、 吡啶-4-硼酸 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以0.55 g的产率得到4-pyridin-4-yl-2,3-dihydro-1H-indole
  参考文献：
  名称：

  [EN] CYANOPYRROLIDINES AS DUB INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] CYANOPYRROLIDINES EN TANT QU'INHIBITEURS DES DUB POUR LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及新型化合物和制备去泛素酶（DUBs）抑制剂的方法。具体而言，本发明涉及抑制泛素C-末端水解酶L1（UCHL1）和泛素C-末端水解酶30或泛素特异性肽酶30（USP30）。本发明还涉及在治疗癌症和涉及线粒体功能障碍的疾病中使用DUB抑制剂。本发明的化合物包括具有以下式（I）或其药用可接受盐的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8和R9如本文所定义。

  公开号：

  WO2017009650A1

文献信息

• NOVEL PYRIMIDINE DERIVATIVES, PREPARATION THEREOF, AND PHARMACEUTICAL USE THEREOF AS AKT(PKB) PHOSPHORYLATION INHIBITORS
  申请人：Brollo Maurice

  公开号：US20130274253A1

  公开（公告）日：2013-10-17

  The present invention relates to novel chemical compounds derived from pyrimidines, to the method for preparing same, to the novel intermediates obtained, to the use thereof as drugs, to the pharmaceutical compositions containing same, and to the therapeutic use thereof as AKT inhibitors.

  本发明涉及从嘧啶衍生的新化合物，以及制备该化合物的方法，获得的新中间体，将其用作药物的用途，含有该化合物的药物组合物，以及将其作为AKT抑制剂的治疗用途。
• Pyrimidine derivatives, preparation thereof, and pharmaceutical use thereof as akt(pkb) phosphorylation inhibitors
  申请人：Brollo Maurice

  公开号：US09133168B2

  公开（公告）日：2015-09-15

  The present invention relates to novel chemical compounds derived from pyrimidines, to the method for preparing same, to the novel intermediates obtained, to the use thereof as drugs, to the pharmaceutical compositions containing same, and to the therapeutic use thereof as AKT inhibitors.

  本发明涉及从嘧啶衍生的新化学化合物，制备方法，获得的新中间体，作为药物的用途，包含它们的制药组合物，以及作为AKT抑制剂的治疗用途。
• THERAPEUTIC AGENT FOR TAUOPATHIES
  申请人：Sumitomo Pharma Co., Ltd.

  公开号：EP4104861A1

  公开（公告）日：2022-12-21

  The present invention is to provide a medicament for treating and/or preventing tauopathy by activating the voltage-gated sodium channel (Nav). The present invention relates to a medicament for treating and/or preventing tauopathy, comprising a Nav activator as an active ingredient.

  本发明提供了一种通过激活电压门控钠通道（Nav）治疗和/或预防tau病的药物。本发明涉及一种治疗和/或预防tau病的药物，其包括Nav激活剂作为活性成分。
• NOUVEAUX DERIVES DE PYRIMIDINES, LEUR PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE COMME INHIBITEURS DE PHOSPHORYLATION D'AKT(PKB)
  申请人：SANOFI

  公开号：EP2658844B1

  公开（公告）日：2016-10-26
• US9133168B2
  申请人：——

  公开号：US9133168B2

  公开（公告）日：2015-09-15